1WYX

The Crystal Structure of the p130Cas SH3 Domain at 1.1 A Resolution

1WYX の概要

• エントリーDOI: 10.2210/pdb1wyx/pdb
• 分子名称: CRK-associated substrate, 1,2-ETHANEDIOL, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: beta sheets, cell adhesion
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell junction, focal adhesion (By similarity): P56945
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 15610.20

構造登録者

Wisniewska, M.,Bossenmaier, B.,Georges, G.,Hesse, F.,Dangl, M.,Kuenkele, K.P.,Ioannidis, I.,Huber, R.,Engh, R.A. (登録日: 2005-02-17, 公開日: 2005-04-26, 最終更新日: 2024-03-13)

主引用文献

Wisniewska, M.,Bossenmaier, B.,Georges, G.,Hesse, F.,Dangl, M.,Kunkele, K.P.,Ioannidis, I.,Huber, R.,Engh, R.A.
The 1.1 A resolution crystal structure of the p130cas SH3 domain and ramifications for ligand selectivity
J.Mol.Biol., 347:1005-1014, 2005

PubMed Abstract: The Crk-associated tyrosine kinase substrate p130cas (CAS) is a docking protein containing an SH3 domain near its N terminus, followed by a short proline-rich segment, a large central substrate domain composed of 15 repeats of the four amino acid sequence YxxP, a serine-rich region and a carboxy-terminal domain, which possesses consensus binding sites for the SH2 and SH3 domains of Src (YDYV and RPLPSPP, respectively). The SH3 domain of CAS mediates its interaction with several proteins involved in signaling pathways such as focal adhesion kinase (FAK), tyrosine phosphatases PTP1B and PTP-PEST, and the guanine nucleotide exchange factor C3G. As a homolog of the corresponding Src docking domain, the CAS SH3 domain binds to proline-rich sequences (PxxP) of its interacting partners that can adopt a polyproline type II helix. We have determined a high-resolution X-ray structure of the recombinant human CAS SH3 domain. The domain, residues 1-69, crystallized in two related space groups, P2(1) and C222(1), that provided diffraction data to 1.1 A and 2.1 A, respectively. The crystal structure shows, in addition to the conserved SH3 domain architecture, the way in which the CAS characteristic amino acids form an atypically charged ligand-binding surface. This arrangement provides a rationale for the unusual ligand recognition motif exhibited by the CAS SH3 domain. The structure enables modelling of the docking interactions to its ligands, for example from focal adhesion kinase, and supports structure-based drug design of inhibitors of the CAS-FAK interaction.

PubMed: 15784259
DOI: 10.1016/j.jmb.2005.02.017

実験手法

X-RAY DIFFRACTION (1.14 Å)